Acute kidney injury (AKI) is one of the most common and severe nephropathy syndromes in clinical practice and also one of the most common serious complications after organ transplantation, with high incidence and fatality. Iron is an essential trace element in the body. Ferroptosis is a form of programmed cell death induced by the accumulation of iron-mediated lipid peroxidation, and its occurrence is closely related to iron metabolism, lipid metabolism, amino acid metabolism and multiple signaling pathways. Recent studies have shown that ferroptosis plays a key role in the occurrence and development of AKI and provides therapeutic targets for AKI. This article summarizes the regulatory mechanism of ferroptosis and its role in AKI, as well as the compounds that play an important role in the prevention and treatment of AKI by inhibiting ferroptosis, providing new ideas for the future treatment and research of AKI.

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2^f/fLyz2-Cre^+/- mice. Synovial inflammation and M1 polarization were improved in GRK2^f/fLyz2-Cre^+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1⁺ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

Objective To explore the prevalence rate and related factors of urban and rural residents with hyperuricemia (HUA). Methods A total of 360 subjects in physical examination department of Sanliusan Hospital from January 2020 to January 2023 were selected and divided into urban residents and rural residents according to their permanent residence addresses, and the demographic information, living habits and underlying diseases were collected. Fasting blood glucose (FBG), serum uric acid (SUA), body mass index (BMI) and triglyceride (TG) were measured. The risk factors of HUA were analyzed by logistics regression analysis. Results The incidence rates of HUA in urban and rural residents were 12.18% and 12.88%. There were statistically significant differences in education level, occupation, BMI, sleep time, alcohol drinking, FBG and TG between urban and rural residents (all P<0.05). Logistics regression analysis showed that male, BMI>24 kg/m², alcohol drinking and chronic kidney disease were independent risk factors for HUA occurrence among urban residents (all P<0.05). Chronic kidney disease, FBG≥7.0 mmol/L and TG≥2.3 mmol/L were independent risk factors for hyperuricemia occurrence among rural residents (all P<0.05). Conclusion Rural residents should strengthen health education and blood glucose and lipid control, and urban residents should pay more attention to reasonable exercise, control alcohol consumption and reduce HUA occurrence.

Objective:To study the impact of financial compensation on the competitive strategy selection of public hospitals.Methods:Based on the quality and cost strategy selection framework of public hospitals,the evolutionary game model of strategy selection of secondary and tertiary public hospitals was established,and the influence of different financial compensation methods on the competitive strategy selection of public hospitals was analyzed by matlab simulation.Results:The more public hospitals choose the optimal strategy,the faster they reach the evolutionary stable state of the optimal strategy.The financial compensation of the same unit can change the competitive strategy choice tendency of the secondary hospitals.Regardless of the tertiary or secondary public hospitals,the impact of the compensation quality strategy is greater than the compensation cost policy,but the over-compensation quality strategy will cause the secondary hospitals to deviate from the optimal strategy.The impact of hospital competition costs on secondary public hospitals is much greater than that of tertiary public hospitals.Conclusion:To clarify the positioning and strategy of secondary and tertiary hospitals from the policy;financially increase the investment in the quality construction of tertiary public hospitals and increase the investment in the management level of secondary hospitals;strengthen supervision and management,guide the hospital reasonable competition.

BackgroundAlcohol use disorder （AUD） is a common chronic and relapsing psychiatric disorders. Identifying severe AUD early and intervening promptly is crucial to prevent irreversible harm. Currently， the assessment of AUD severity primarily relies on psychiatric examination by clinicians， and there is limited research on the factors influencing AUD severity and the development of prediction models. ObjectiveTo analyze the factors influencing AUD severity， and construct a risk prediction model to aid in the assessment of disease progression in AUD patients. MethodsA retrospective analysis was conducted on 1 358 first-time hospitalized patients admitted to Nanning Fifth People's Hospital from January 1， 2017 to December 31， 2022. These patients met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） criteria for AUD. Basic patient data was collected， and the patients were divided into two groups based on disease severity： mild-moderate group （n=330） and severe group （n=1 028）. The patients were randomly divided into training and test sets in a 7∶3 ratio. A Logistic regression model was constructed in the training set， and the predictive ability of the model for disease severity was evaluated using the receiver operating characteristic （ROC） curve in the test set. ResultsCompared with the mild-moderate group， the severe group had a higher proportion of patients living in urban areas （χ²=7.804）， were farmers （χ²=17.991）， had a higher frequency of alcohol consumption （more than 1 to 2 drinks/day） （χ²=35.267）， had a higher age at first drinking （t=-3.858）， had a greater number of comorbid somatic disorders （Z=-22.782）， and had higher proportions of γ-Glutamyl transpeptidase （χ²=259.940） and total bilirubin abnormalities （χ²=148.552） （P<0.01）. Logistic analysis conducted in the training set showed that being a farmer （OR=2.024， 95% CI： 1.352~3.029）， having an older age at first drinking （OR=1.075， 95% CI： 1.025~1.129）， drinking outside of mealtimes （OR=3.988， 95% CI： 2.408~6.606）， having total bilirubin abnormalities （OR=1.034， 95% CI： 1.000~1.069）， and having more comorbid somatic diseases （OR=4.386， 95% CI： 2.636~7.298） were identified as risk factors for disease severity in AUD patients. The area under curve （AUC） for this model in the test set was 0.906. ConclusionIn psychiatric hospitals， being a farmer， having an older age at first drinking， drinking outside of mealtimes， having abnormal total bilirubin levels， and having comorbidities with somatic illnesses may be risk factors for severe AUD.

The mechanism of tinnitus remains undear.Currently,in addition to tinnitus induced by ear disea-ses,various systems of the body are also involved in the pathogenesis of tinnitus.Obstructive sleep apnea hypopnea syndrome(OSAHS)may be related to tinnitus,which has garnered increasing attention in recent years.This article reviews the latest research progress on the occurrence and possible mechanism of tinnitus in OSAHS,shedding new light on the treatment of tinnitus.

Objective To investigate the effect of tumor-infiltrating B cells on the therapeutic efficacy of programmed death ligand-1[PD-(L)1]inhibitors and elucidate the potential mechanisms.Methods Based on immunotherapy cohorts for melanoma patients in public databases,the relationship of B cells with progression-free survival (PFS) and response to immune checkpoint inhibitors treatment was analyzed.TC-1 and B16-OVA cells were implanted subcutaneously and in the liver in 6-8-week-old female C57BL/6 mice to establish tumor xenograft models.The effect of B cell clearance on PD-(L)1 therapy was compared.Flow cytometry was performed on the 15th day of TC-1 tumor microenvironment (TME)to confirm the number,function and phenotypic changes of T cells.Flow cytometry and quantitative real-time polymerase chain reaction (qPCR)were used to detect B cell surface molecules and cytokines.Results Based on ERP105482 data from the ICBatlas public database,high CD19 expression in the tumors was associated with longer PFS in melanoma patients (753 vs 95 d,HR=0.3,95％CI:0.13～0.65,P=0.003).B cells were significantly enriched in immunotherapy-responsive patients (P=0.01).In a mouse TC-1 liver-loaded tumor model,PD-(L)1 antibody treatment reduced tumor mass (P<0.01),whereas B-cell clearance attenuated the therapeutic efficacy.B cells enhanced PD-(L)1 antibody treatment by promoting T cell infiltration and function,and the treatment resulted in changes in B cell subsets,as evidenced by an increase in PD-1 low-expressing subsets (P<0.01).Conclusion After PD-(L)1 treatment,a decrease in PD-1 expression on B cell subsets might be one of the potential mechanisms by which B cells enhance the efficacy of PD-(L)1 therapy.

Objective To explore the effect of cancer related anemia on the abundance of SARS-CoV-2 specific memory CD8+T cells in peripheral blood.Methods A total of 34 HLA-A*11∶01 positive patients with middle-and late-stage tumors admitted in the Rocket Force Medical Center of PLA from June to July 2023 were enrolled in this study.According to hemoglobin(HGB)level,they were divided into non anemia group(≥120 g/L,n=14),mild anemia group(90～120 g/L,n=14),and moderate to severe anemia group(＜90 g/L,n=6).After their peripheral blood mononuclear cells were isolated,memory CD8+T cells were stimulated by the epitopes of SARS-CoV-2 and then expanded.Positive epitopes were screened using enzyme-linked immunosorbent spot(ELISP OT)assay,and then MHC-peptide Tetramers were constructed.The proportion and number of Tetramer+cells and the number of ELISPOT spots were detected in the expanded cells to reflect the abundance of SARS-CoV-2 specific memory CD8+T cells.The relevance of patients'HGB level with the proportion and number of Tetramer+cells and the number of ELISPOT spots was analyzed.The differences of the proportion and number of Tetramer+cells and the number of ELISPOT spots was analyzed in different groups.Results Among the 34 patients,there were 25 males and 9 females,at an age range of 36～78(median 57)years.The proportion and number of Tetramer+cells and the number of ELISPOT spots were positively correlated with HGB level(P＜0.05).The proportion and number of Tetramer+cells and the number of ELISPOT spots were significantly decreased in patients with moderate to severe anemia than the non anemia patients(P＜0.05).Conclusion The abundance of SARS-CoV-2 specific memory CD8+T cells in peripheral blood is positively correlated with patients'HGB level,indicating that CRA may increase the susceptibility of patients to viruses by reducing the abundance of memory CD8+T cells in peripheral blood.

Objective: To establish an inducible macrophage-specific knockout G protein-coupled receptor kinase 2 ( GRK2) gene ( GRK2flox / flox Lyz2-CreERT + ) mice model． Methods: GRK2flox / flox Lyz2-CreERT + mice were constructed based on Cre / LoxP system．The genotypes of GRK2flox / floxLyz2-CreERT + mice were identified by PCR amplification and agarose gel electrophoresis．After the mice were sacrificed by carbon dioxide method，the expression of GRK2 in bone marrow-derived macrophages ( BMDMs) and peritoneal macrophages ( PMs) was detected by Western blot．Immunofluorescence was used to detect GRK2 expression in mouse brain，heart and spleen macrophages．The M1 / M2 ratio in PMs induced by prostaglandin E2 (PGE2) was analyzed by flow cytometry. Results: The results of genotype identification showed that the mice with a band at 355 bp in the length of the flox amplification product and a band at 355 bp in the length of the Cre amplification product were GRK2flox / floxLyz2-CreERT + mice．Western blot results showed that GRK2 expression in BMDMs and PMs of GRK2flox / floxLyz2-CreERT + mice decreased compared with GRK2flox / flox mice(P＜0. 01) ．Immunofluorescence results showed that GRK2 expression decreased in the brain，heart and spleen of GRK2flox / floxLyz2-CreERT + mice compared with GRK2flox / flox mice (P < 0. 01) ．Flow cytometry showed that compared with GRK2flox / flox mice，there was no significant difference in the proportion of CD86 / CD206 in the PMs of GRK2flox / floxLyz2-CreERT + mice．Under PGE2 ( 10 μmol / L) stimulation， the proportion of CD86 / CD206 in GRK2flox / floxLyz2-CreERT + mice PMs increased (P ＜0. 01) ．The proportion of CD86 / CD206 in the PMs of GRK2flox / flox mice was higher than that of GRK2flox / floxLyz2-CreERT + mice(P＜0. 01) . Conclusion In this study，GRK2flox / floxLyz2-CreERT + mice model was successfully constructed，and the mice promoted PGE2-induced polarization of PMs to M2-type macrophages compared with control mice.

Objective    To evaluate the short-term therapeutic effect of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of acute type A aortic dissection (ATAAD). Methods    From November 2019 to July 2020, 28 patients with ATAAD were treated by extended adventitial inversion with graft eversion anastomosis technique in the Department of Cardiovascular Surgery, Dalian Municipal Central Hospital, including 19 males and 9 females, aged 60.11±11.11 years. The intima of the ascending aorta was trimed to 5 mm above the sinotubular junction. The adventitia of the ascending aorta was longitudinally cut to the reserved intima margin along the junction of the three aortic valves. The extended adventitial inversion was sutured continuously, no coronary sinus was sutured over the aortic annulus, and the left and right coronary sinus was sutured above the coronary ostium. The anastomotic graft was everted and inserted into the aortic lumen, and the everted graft was continuously sutured at the level of sinotubular junction which was 5 mm away from the edge of graft. Results    There was no intraoperative death, intractable root hemorrhage, residual root false lumen, root dilatation, anastomotic hematoma or other complications. There was no recurrence of the pain in the back of all patients, and the results of the CT angiography were not significantly changed. In 22 patients with no regurgitation, only 1 (4.55%) patient had a mild regurgitation. In 6 patients with mild aortic regurgitation, the disappearance rate of regurgitation was 50.0% (3/6). Conclusion    The treatment of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of aortic dissection eliminates the residual dissection at the root. The anastomotic hemorrhage is prevented, the root structure of aortic dissection is reconstructed and strengthened, the root function is restored, and the possible expansion of the root is prevented. The short-term results are satisfactory.